Natural Product: NPC602776

Natural Product IDNPC602776
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QXPNJMHRUZCEAP-UXBSLASESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2012519
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey QXPNJMHRUZCEAP-UXBSLASESA-N
Standard InCHI InChI=1S/C19H24O7/c1-11-5-3-7-14(20)18(23)15(21)8-4-6-12-9-13(25-2)10-16(22)17(12)19(24)26-11/h3,7,9-11,15,18,21-23H,4-6,8H2,1-2H3/b7-3-/t11-,15-,18+/m0/s1
SMILES COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=CC[C@H](C)OC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.15 Volume:   365.78
?
Van der Waals volume.
Dense:   0.996 LogP:   1.739
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.999
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.711
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   21.0
TPSA:   113.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.648 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.159 Fsp3:   0.474
MCE-18:   52.5
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.508 Fluc inhibitor:   0.659
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.142
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.453
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.094 Promiscuous compounds:   0.765

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.069 MDCK Permeability:   -4.696
Pgp-inhibitor:   0.229 Pgp-substrate:   0.082
PAMPA:   0.759
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.133
20% Bioavailability (F20%):   0.081 30% Bioavailability (F30%):   0.674
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.646
Plasma Protein Binding (PPB):   81.871% Volume Distribution (VD):   -0.043
Fu: 12.172%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.354
BSEP inhibitor:   0.681

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.276 CYP2C9-substrate:   0.146
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.246
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.988
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.131 Half-life (T1/2):  1.878

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.218
Human Hepatotoxicity (H-HT):  0.798 Drug-induced Liver Injury (DILI):  0.931
AMES Toxicity:  0.838 Rat Oral Acute Toxicity:  0.391
Maximum Recommended Daily Dose:  0.875 Skin Sensitization:  1.0
Carcinogencity:  0.751 Eye Corrosion:  0.093
Eye Irritation:  0.931 Respiratory Toxicity:  0.804
Drug-induced Neurotoxicity:  0.851 Ototoxicity:  0.258
Hematotoxicity:  0.154 Drug-induced Nephrotoxicity:  0.973
Genotoxicity:  0.992 RPMI-8226 Immunitoxicity:  0.327
A549 Cytotoxicity:  0.885 Hek293 Cytotoxicity:  0.696
BCF:   0.857
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.569
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.867
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.242
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO55922 Phoma sp. (ATCC 74403) Genus Didymellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1438 Individual protein Insulin-like growth factor I receptor Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT3107 Individual protein Rho-associated protein kinase 2 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1690 Individual protein Dual specificity mitogen-activated protein kinase kinase 2 Homo sapiens IC50 = 15.0 nM PMID[24900250]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens IC50 = 57.0 nM PMID[24900250]
NPT1440 Individual protein Tyrosine-protein kinase JAK3 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT2729 Individual protein Tyrosine-protein kinase ABL Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens GI50 = 270.0 nM PMID[31513411]
NPT2573 Individual protein Vascular endothelial growth factor receptor 3 Homo sapiens IC50 = 0.73 nM PMID[31513411]
NPT3258 Individual protein Mixed lineage kinase 7 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3283 Individual protein MAP kinase-interacting serine/threonine-protein kinase MNK1 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3355 Individual protein TGF-beta receptor type II Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT2572 Individual protein Ephrin type-B receptor 4 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1432 Individual protein Serine/threonine-protein kinase Aurora-A Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT3364 Individual protein Protein kinase C mu Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3213 Individual protein MAP kinase signal-integrating kinase 2 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3442 Individual protein Mitogen-activated protein kinase kinase kinase 7 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3319 Individual protein Dual specificity mitogen-activated protein kinase kinase 4 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens IC50 = 62.0 nM PMID[25456387]
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 = 750.0 nM PMID[19394221]
NPT3213 Individual protein MAP kinase signal-integrating kinase 2 Homo sapiens IC50 = 60.0 nM PMID[33892273]
NPT3227 Individual protein Fibroblast growth factor receptor 3 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT3283 Individual protein MAP kinase-interacting serine/threonine-protein kinase MNK1 Homo sapiens IC50 = 325.0 nM PMID[33892273]
NPT1371 Individual protein Cyclin-dependent kinase 2 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT2573 Individual protein Vascular endothelial growth factor receptor 3 Homo sapiens GI50 = 50.0 nM PMID[31513411]
NPT1479 Individual protein Stem cell growth factor receptor Homo sapiens IC50 = 303.0 nM PMID[24900250]
NPT3370 Individual protein Tyrosine-protein kinase receptor RET Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens IC50 = 2.0 nM PMID[24900250]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens IC50 = 11.0 nM PMID[25456387]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens IC50 = 36.0 nM PMID[25456387]
NPT1691 Individual protein Dual specificity mitogen-activated protein kinase kinase 6 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens IC50 = 6.34 nM PMID[28103025]
NPT1691 Individual protein Dual specificity mitogen-activated protein kinase kinase 6 Homo sapiens IC50 = 388.2 nM PMID[28103025]
NPT2575 Individual protein Platelet-derived growth factor receptor beta Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT3020 Individual protein Platelet-derived growth factor receptor alpha Homo sapiens IC50 = 2.38 nM PMID[24900250]
NPT1656 Individual protein Protein kinase N1 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1612 Individual protein MAP kinase-activated protein kinase 5 Homo sapiens IC50 = 640.0 nM PMID[24900250]
NPT1703 Individual protein cAMP-dependent protein kinase alpha-catalytic subunit Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens IC50 = 1.8 nM PMID[31513411]
NPT2573 Individual protein Vascular endothelial growth factor receptor 3 Homo sapiens IC50 = 1.13 nM PMID[28103025]
NPT3365 Individual protein Serine/threonine-protein kinase D2 Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT283 Individual protein MAP kinase p38 alpha Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 = 6200.0 nM PMID[24900250]
NPT1690 Individual protein Dual specificity mitogen-activated protein kinase kinase 2 Homo sapiens IC50 = 8.16 nM PMID[28103025]
NPT3366 Individual protein Protein kinase C nu Homo sapiens Inhibition > 80.0 % PMID[28103025]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens IC50 = 2.9 nM PMID[31513411]
NPT3218 Individual protein Ephrin type-A receptor 4 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT286 Individual protein Receptor protein-tyrosine kinase erbB-2 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1337 Individual protein Hepatocyte growth factor receptor Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1689 Individual protein Tyrosine-protein kinase JAK1 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT3246 Individual protein Tyrosine-protein kinase JAK2 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens GI50 = 140.0 nM PMID[31513411]
NPT3304 Individual protein Serine/threonine-protein kinase receptor R3 Homo sapiens IC50 = 125.0 nM PMID[28103025]
NPT3304 Individual protein Serine/threonine-protein kinase receptor R3 Homo sapiens Inhibition n.a. n.a. % PMID[28103025]
NPT3213 Individual protein MAP kinase signal-integrating kinase 2 Homo sapiens IC50 n.a. n.a. n.a. PMID[24900250]
NPT282 Individual protein MAP kinase ERK2 Homo sapiens IC50 = 950.0 nM PMID[24900250]
NPT1650 Individual protein Tyrosine-protein kinase receptor FLT3 Homo sapiens IC50 = 1.59 nM PMID[28103025]
NPT1661 Individual protein ALK tyrosine kinase receptor Homo sapiens IC50 = 763.0 nM PMID[24900250]
NPT3276 Individual protein Tyrosine-protein kinase TYK2 Homo sapiens IC50 = 4100.0 nM PMID[24900250]
NPT3259 Individual protein Tyrosine-protein kinase ZAP-70 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT1659 Individual protein Tyrosine-protein kinase receptor UFO Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT2574 Individual protein Insulin receptor Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT3357 Individual protein Protein kinase N2 Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT29259 Single protein TGF-beta receptor type-1 Mus musculus Inhibition n.a. n.a. % PMID[28103025]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IC50 > 10000.0 nM PMID[24900250]
NPT29738 Single protein Serine/threonine-protein kinase receptor R3 Mus musculus Inhibition n.a. n.a. % PMID[28103025]
NPT833 Individual protein Tyrosine-protein kinase BTK Homo sapiens IC50 > 10000.0 nM PMID[24900250]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6374 Cell line BaF3 Mus musculus GI50 = 1700.0 nM PMID[31513411]
NPT111 Cell line K562 Homo sapiens GI = 69.7 % PMID[25456387]
NPT1649 Cell line MV4-11 Homo sapiens IC50 = 10.0 nM PMID[25456387]
NPT1649 Cell line MV4-11 Homo sapiens GI = 99.7 % PMID[25456387]
NPT28438 Unchecked Unchecked n.a. IC50 > 10000.0 nM PMID[24900250]
NPT28438 Unchecked Unchecked n.a. INH = 4.0 nM PMID[24900361]
NPT28438 Unchecked Unchecked n.a. IC50 = 4000.0 nM PMID[32652407]
NPT28833 No target No relevant target n.a. Activity < 1.0 % PMID[24900250]
NPT28438 Unchecked Unchecked n.a. IC50 = 4.0 nM PMID[19394221]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1180.0 nM PMID[25456387]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI = 86.0 % PMID[25456387]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI = 81.5 % PMID[25456387]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC602776 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.6571 Remote Similarity NPC73411
0.6571 Remote Similarity NPC215711
0.6571 Remote Similarity NPC600572
0.6571 Remote Similarity NPC609200
0.6571 Remote Similarity NPC610004
0.6389 Remote Similarity NPC99381
0.5217 Remote Similarity NPC469542
0.5132 Remote Similarity NPC215921
0.5079 Remote Similarity NPC145442
0.5065 Remote Similarity NPC86373
0.5065 Remote Similarity NPC277426

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC602776 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data